The elucidation of the mechanism and control of oxidative metabolism of drugs, steroids, carcinogenic agents and other xenobiotics is the goal of this research program. The kinetics of formation and the chemistry of key intermediates during oxygen activation will be evaluated using sensitive spectrophotometric techniques as well as other biophysical methods. Changes in the pattern of drug metabolism and cytochrome P-450 induction will be studied in vivo in experimental animals as a function of drug or chemical treatment, in addition to protein or mineral malnutrition. Particular emphasis will be placed on a determination of the effects of multiple drug therapy on cytochrome P-450 induction and oxidative drug metabolism. Efforts to extend the methodology to human tissue will be continued so that a comparison of the properties of cytochrome P-450 and possible genetic variations in drug metabolism can be made. Use of cellular and subcellular systems will be employed to monitor the relationship of drug and steriod metabolism to glycolysis, fatty acid biosynthesis, and other metabolic functions within the cell.